After receiving his law degree in Paris, Brisson joined the ranks of the opposition to the emperor Napoleon III (reigned 1852–70). He contributed regularly to a number of republican journals, most notably L'Avenir (1854–55) and Le Temps (1864), of which he was an editor. After serving as deputy mayor of Paris from Sept. 4, 1870, he was elected, on his second attempt, to the National Assembly as a deputy from the capital in February 1871. He represented a Parisian district from 1876 to 1902 and then was elected from the Bouches-du-Rhône département from 1902 to 1912.

Brisson was influential in parliamentary circles and served the Republican Union in various offices, including the chairmanship. In the late 1870s he was head of the budget commission. When the Jules Ferry government fell in March 1885, he formed his first Cabinet, which lasted only until Dec. 29, 1885. After service as chairman of the commission that investigated charges of bribery against deputies in the Panama Scandal, he headed a second ministry. Once again it was brief, from June 28 to Oct. 25, 1898, when it fell because his war minister, General Jules Chanoine, defied the Cabinet in expressing his belief in the guilt of Alfred Dreyfus in the Dreyfus affair. In 1900 Brisson was elected president of the Chamber of Deputies (reelected in 1906 and 1912) and gave vigorous support to the movement that achieved a separation of the affairs of church and state.